The survival and function of transfused platelets is very sensitive to storage pH. The first generation of plastic blood storage containers were made of polyvinylchloride which inhibited gas exchange with the atmosphere. This tended to cause acidic conditions (pH less than 6). Investigations revealed that these bags became acidic due to the entrapment of carbon dioxide in the bags while lactic acid accumulated from anaerobic metabolic processes occurring within the stored platelets. This gradual decrease of pH due to the presence of increasing amounts of lactic acid and entrapped carbon dioxide caused damage to the platelets, more specifically to the membrane of the cells. As a result, the transfused platelets were hemostatically ineffective and were rejected by the body of the recipient very shortly after transfusion.
This storage problem led to the development of second generation storage containers made of more gas permeable polyolefin materials. Examples of the so-called second generation storage containers are those made by Baxter-Travenol, Fenwal, and Cutter. These second generation storage containers as now available are commonly polymerized alpha olefins such as polyethylene, etc. Because they have the advantage of being gas permeable, there is the expectation that carbon dioxide can be released in compensation for the amount of lactic acid production of the stored platelets. Thus the pH will not fall. While these bags work for their intended purpose, they create an additional problem. Namely, over compensation of carbon dioxide release. Thus, the bags give up carbon dioxide so rapidly that in fact alkaline environmental conditions are induced within the storage bags. Alkaline conditions (greater than 7.5) are as damaging to platelets as acid pH. In particular, alkaline pH leads to a dramatic drop off in survival after transfusion caused by modification of the platelet membrane. This is probably due to the coating of transfused platelets with antibody and their destruction in the patient's spleen.
In short, the solving of the problem of acidic conditions created by bags which inhibit gas exchange creates the problem of too much gas exchange which tends to alkaline conditions that are just as damaging to platelets.
Accordingly, it is an object of the present invention to provide a non-toxic, non-harmful additive for use with blood storage containers which avoids both extremes of pH and instead provides a pH stable stored blood product.
Another object of the present invention is to provide a method of controlling pH of stored blood platelets.
A further object of the present invention is to provide a method of modulating lactic acid production of stored platelets by using non-toxic additives, with the result being high survival rate of stored platelets ready for use with transfused patients.
A further objective of the present invention is to employ a lactic acid stimulator to modulate lactic acid production of stored platelets which is 2,5-anhydro-D-mannitol or a nontoxic, non-harmful, derivative thereof.
The method and manner of accomplishing each of the above objectives of the present invention will become apparent from the detailed description which follows hereinafter.